CN102334465A - Establishment method of animal model for acute Stanford A-type aortic dissection (AD) accompanied with MODS (multiple organ dysfunction syndrome) - Google Patents
Establishment method of animal model for acute Stanford A-type aortic dissection (AD) accompanied with MODS (multiple organ dysfunction syndrome) Download PDFInfo
- Publication number
- CN102334465A CN102334465A CN2010106088198A CN201010608819A CN102334465A CN 102334465 A CN102334465 A CN 102334465A CN 2010106088198 A CN2010106088198 A CN 2010106088198A CN 201010608819 A CN201010608819 A CN 201010608819A CN 102334465 A CN102334465 A CN 102334465A
- Authority
- CN
- China
- Prior art keywords
- aorta
- group
- mods
- experimental group
- time point
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Abstract
The invention provides an establishment method of an animal model for acute Stanford A-type aortic dissection (AD) accompanied with MODS (multiple organ dysfunction syndrome), a use of emodin for preparing a medicine for treating acute Stanford A-type AD accompanied with MODS as well as a viscera protective agent for acute Stanford A-type AD accompanied with MODS. In the invention, an AD surgery method is improved and meanwhile manually controlled hypertension is formed by continuously pumping adrenaline into veins so as to promote expansion of the AD stripping range and accelerate disease progression, thus acute Stanford A-type AD accompanied with MODS can be rapidly formed so as to successfully make the model. The animal model for acute Stanford A-type AD accompanied with MODS creates conditions for further deep research in application foundation and intervention treatment.
Description
Technical field
The present invention relates to a kind of method for building up of acute Stanford A type dissection of aorta companion MODS animal model.
Background technology
Acute dissection of aorta (aortic dissection; AD) be meant after tear in the sustainer middle level that blood gets into false chamber through the tearing port of film in the inner membrance, it is the critical acute disease of department of cardiovascular surgery; Progress is fast; Lethality is high, and per hour lethality can be up to 50% in 1%, 48 hour approximately for early stage case fatality rate.The somatotype of dissection of aorta has a variety of, with regard to guiding clinical treatment, and the most frequently used also most worthy of Stanford somatotype.Stanford A type dissection of aorta refers to that pathology is involved aorta ascendens companion or without involving descending aorta, and Stanford Type B dissection of aorta refers to that pathology only involves descending aorta.After dissection of aorta took place, artery blood flow continued to get into false chamber, and carrying out property of arterial wall is peeled off, and false chamber continues to enlarge.False cavity pressure increases, and volume increases, and oppresses true chamber and makes the forward direction blood flow reduce the far-end ischemic; Perhaps oppress the sustainer important branch, cause the vitals ischemic; Other secondary lesions in addition, (multiple organ dysfunction syndrome, MODS), MODS is one of major reason that causes death finally to cause the multiple organ dysfunction syndrome.The pertinent literature report that MODS research takes place about dissection of aorta is few; But other correlative studys that cause MODS serious disease (like acute necrotic pancreatitis etc.) show; Systemic inflammatory response syndrome (systemic inflammatory response syndrome, the prelude of the MODS that SIRS) usually causes for any reason.Therefore, setting up the animal model of an acute AD companion MODS, is the important foundation research work of research inflammatory reaction effect in AD and MODS thereof take place, develop.
As far back as nineteen fifty-nine, Blanton FS etc. sets up the AD model with operation method.Along with the development of interventional technique, also there is the scholar to carry out making and the achieving success of AD in recent years with the mode that gets involved.But these models all are confined to Stanford Type B AD, and exist the interlayer tear(ing) strength limited, and success rate of operation is not high, are difficult to set up acute Stanford A type AD companion MODS.Present literature search shows; Can simulate the still manque report of animal model of the acute AD companion MODS that clinical onset is anxious, progress is fast, lethality is high; And further investigate the mechanism of acute AD incidence and development; The key link of seeking to intervene, the new technologies of development clinical treatment then presses for and sets up animal model.The method that makes up the dissection of aorta animal model can be traced back to nineteen fifty-two the earliest, and the method that Blanton FS etc. open chest with performing the operation for the first time attempts setting up sandwich mould.They expose sustainer through opening chest, and the surgical incision aorta wall carries out passivity with the aorta wall middle level of otch far-end and separates, and be seamed to the holostrome of proximal arterial to the far-end sarcocyte, thereby causes the aorta clamp layer model.Though the method successfully copies the model of dissection of aorta, the false chamber of the interlayer that duplicates out is shorter, and the success rate of operation is not high, and MODS does not occur together.After this decades, modelling is with reference to the method for Blanton FS operation and makes dissection of aorta, and model does not have big development.Along with the raising of interventional technique, more and more scholars begins to adopt the method to make dissection of aorta.2002, two Da Tang of army respected the method for trial usefulness interventions such as east and duplicate sandwich mould.They are material with the puncture needle that can adjust angle; Under X line perspective helps; Puncture needle is directed into aorta pectoralis through laboratory animal arteria iliaca communis or abdominal aorta, and the angle through the adjustment puncture needle makes punctures aortic tunica media and injecting normal saline and elastin enzyme make interlayer; The success rate that this kind method is made sandwich mould is lower, and the interlayer of making is obvious inadequately; And this method needs good interventional technique, and is higher to operator's specification requirement, careless slightlyly can cause arteriorrhexis.The someone adopts out chest to expose sustainer in addition, separates the artery gap, separates the gap of artery then with the Forgarty catheter-balloon, forms artery dissection.
Though forefathers have carried out good try to the making of aorta clamp layer model, these models all exist interlayer to tear limited length, and interlayer is made into the not high shortcoming of power, and these models are Stanford Type B interlayer.Relevant report is not seen in making for A type interlayer, and the MODS that occurs together after making about interlayer does not more have relevant record.Therefore, the application foundation of acute dissection of aorta and clinical research press for foundation can the acute Stanford A of mimic human type dissection of aorta pathological anatomy and physiopathologic experimental animal model.
Summary of the invention
Technical scheme of the present invention has provided a kind of method for building up of acute Stanford A type dissection of aorta companion MODS animal model.Another technical scheme of the present invention has provided a kind of method of the acute Stanford A type dissection of aorta companion of treatment MODS medicine and new purposes of medicine archen of screening.
The invention provides a kind of method for building up of acute Stanford A type dissection of aorta companion MODS animal model, it comprises the steps:
A, get experimental dog, expose aorta ascendens;
B, at the position of the about 2cm of aorta ascendens initial part far-end, sidewall pincers stringer clamp sustainer sidewall about 1/2 week the footpath, wide 1/2 of the aorta ascendens Zhou Jing that reaches of film in roundlet blade transection adventitia and the part; Find middle intermembrane space, unclamp the sidewall pincers, use intermembrane space in the Wen Shi tip clamp part edge, softly separate the about 1cm of lengthwise to the distal end passivity;
The Φ 2.5mm Micropump that c, insertion connect syringe prolongs pipe, and high pressure is injected physiological saline fast, utilizes the impact strength of physiological saline pressure to enlarge the interlayer scope, until the about 5cm of strip length; Inject elastin enzyme (200u adds 2ml physiological saline) in the false chamber, compressing sustainer otch makes it in false chamber, to keep somewhere about 5 minutes kinds;
D, clamp sidewall pincers once more; Cut the middle film and the inner membrance of internal layer; Aorta lumen is communicated with the external world; Fan-shapedly wipe out film and inner membrance in the interlayer otch distal end part, film in 6-0prolene suturing with thread management otch proximal part aorta wall holostrome and distal end adventitia and the part makes blood can continue to get into false chamber;
E, unclamp sidewall pincers, strengthen sewing up the incision hemostasis once more; Interlayer completes, and successively closes chest, sews up the wall of the chest;
F, connection micro pump, vein pumps into adrenaline rising blood pressure, and the laboratory animal systolic pressure is maintained between 250～260mmHg.
The present invention also provides the purposes of animal model in the medicine of the acute Stanford A type dissection of aorta companion of screening treatment MODS of this method preparation.
The invention provides a kind of method of screening the acute Stanford A type dissection of aorta companion of treatment MODS medicine, comprise the steps:
1., set up acute Stanford A type dissection of aorta companion MODS animal model;
2., drug candidate is applied to animal model;
3., observe the influence situation of drug candidate to acute Stanford A type dissection of aorta companion MODS, and mark, estimate the medicine of the acute Stanford A of potential treatment type dissection of aorta companion MODS.
Wherein, 1. the method for building up of the described acute Stanford A type dissection of aorta companion MODS animal model of step is:
A, get experimental dog, expose aorta ascendens;
B, at the position of the about 2cm of aorta ascendens initial part far-end, sidewall pincers stringer clamp sustainer sidewall about 1/2 week the footpath, wide 1/2 of the aorta ascendens Zhou Jing that reaches of film in roundlet blade transection adventitia and the part; Find middle intermembrane space, unclamp the sidewall pincers, use intermembrane space in the Wen Shi tip clamp part edge, softly separate the about 1cm of lengthwise to the distal end passivity;
The Φ 2.5mm Micropump that c, insertion connect syringe prolongs pipe, and high pressure is injected physiological saline fast, utilizes the impact strength of physiological saline pressure to enlarge the interlayer scope, until the about 5cm of strip length; Inject elastin enzyme (200u adds 2ml physiological saline) in the false chamber, compressing sustainer otch makes it in false chamber, to keep somewhere about 5 minutes kinds;
D, clamp sidewall pincers once more; Cut the middle film and the inner membrance of internal layer; Aorta lumen is communicated with the external world; Fan-shapedly wipe out film and inner membrance in the interlayer otch distal end part, film in 6-0prolene suturing with thread management otch proximal part aorta wall holostrome and distal end adventitia and the part makes blood can continue to get into false chamber;
E, unclamp sidewall pincers, strengthen sewing up the incision hemostasis once more; Interlayer completes, and successively closes chest, sews up the wall of the chest;
F, connection micro pump, vein pumps into adrenaline rising blood pressure, and the laboratory animal systolic pressure is maintained between 250～260mmHg.
Wherein, described medicine is an archen.
The present invention also provides the purposes of archen in acute Stanford A type dissection of aorta companion MODS of preparation treatment and medicine.
The using dosage of archen is 200mg/kg in the described medicine.
The present invention also provides the organ protection agent of a kind of acute Stanford A type dissection of aorta companion MODS, and it is that archen by effective dose is an active component, adds the preparation that acceptable accessories or complementary composition are prepared from.
Wherein, described preparation is an oral formulations.
The present invention is through improvement AD operation preparation method; Continue to pump into adrenaline by vein simultaneously and form Artificial Control property hypertension; Promote the expansion of AD dissection scope and quicken course of disease progress; With the acute Stanford A of quick formation type AD companion MODS is the target of making successful model, and the animal model of the acute Stanford A of the present invention type AD companion MODS creates conditions for further going deep into the research of applied basic research and therapeutic intervention.
Description of drawings
Fig. 1 interlayer is made successfully, and separate in the middle level, and false chamber forms, and the black arrow indication is that interlayer is torn the position, and width is near 1/2 of sustainer Zhou Jing.
Fig. 2 microscopically amplifies 100 times of observations, and visible interlayer is torn and is positioned at the aorta wall middle level.
Fig. 3 microscopically amplifies 400 times of observations, visible aorta wall middle level elastorrhexis, inflammatory cell infiltration.
The gross anatomy of Fig. 4 experimental group is observed
The gross anatomy of Fig. 5 control group is observed
Fig. 6 experimental group microscope is seen and is looked into (* 100)
Fig. 7 control group microscope is seen and is looked into (* 100)
Fig. 8 experimental group microscopic examination (* 400) Fig. 9 control group microscopic examination (* 400)
The gross anatomy of Figure 10 experimental group is observed the gross anatomy of Figure 11 control group and is observed
Figure 12 experimental group microscopic examination (* 100) Figure 13 control group microscopic examination (* 100)
Figure 14 experimental group microscopic examination (* 400) Figure 15 control group microscopic examination (* 400)
The gross anatomy of Figure 16 experimental group is observed the gross anatomy of Figure 17 control group and is observed
Figure 18 experimental group microscopic examination (* 100) Figure 19 control group microscopic examination (* 100)
Figure 20 experimental group microscopic examination (* 400) Figure 21 control group microscopic examination (* 400)
The gross anatomy of Figure 22 experimental group is observed the gross anatomy of Figure 23 control group and is observed
Figure 24 experimental group microscopic examination (* 100) Figure 25 control group microscopic examination (* 100)
Figure 26 experimental group microscopic examination (* 400) Figure 27 control group microscopic examination (* 400)
The gross anatomy of Figure 28 intestines is observed: experimental group Figure 29 organ protection agent group
Figure 30 experimental group microscopic examination (* 100) Figure 31 organ protection agent group microscopic examination (* 100)
Figure 32 experimental group microscopic examination (* 400) Figure 33 organ protection agent group microscopic examination (* 400)
The gross anatomy of Figure 34 lung is observed: experimental group Figure 35 organ protection agent group
Figure 36 experimental group microscopic examination (* 100) Figure 37 organ protection agent group microscopic examination (* 100)
Figure 38 experimental group microscopic examination (* 400) Figure 39 organ protection agent group microscopic examination (* 400)
Embodiment
The method for building up of the acute Stanford A of embodiment 1 the present invention type dissection of aorta companion MODS animal model
1 material
1.1 laboratory animal
18 of healthy adult Beagle dogs, male and female are regardless of, body weight 8～12kg, average 8.95 ± 0.72kg.Every animal divides cage solely to support before the art, and 23～25 ℃ of room temperatures are freely ingested, intake, 12 hours illumination/dark.Dog is provided by West China clinical medicine institute of Sichuan University/West China hospital traditional Chinese medicine safety evaluatio center, and is raised by laboratory animal requirement special messenger by West China clinical medicine institute of Sichuan University/West China hospital Experimental Animal Center Animal House.
1.2 main experiment reagent and medicine
1) liquaemin (biochemical-pharmaceutical factory, Shanghai)
2) Benzylpenicillin sodium salt (North China pharmacy)
3) adrenaline (Shanghai Hefeng Pharmaceutical Co., Ltd.)
4) yellow Jackets (Shanghai chemical reagents corporation)
5) atropine (Haiyang, Hangzhou medication chemistry Co., Ltd)
6) formalin (Xinxiang City Xinlong chemical industry Co., Ltd)
7) equilibrium liquid (Chengdu Li Kang medicine Co., Ltd)
1.3 main experimental instrument and equipment
1) operating theater instruments (Shanghai gold clock medical apparatus corporation, Ltd)
2) electric knife (U.S.'s Willie electric knife)
3) electric suction apparatus (Shanghai medicine equipment industry company)
4) Anesthesia machine (Excel 210 SE Datex-Ohmeda)
5) lung ventilator (S900C Siemens Company)
6) micro-injection pump (Anji, Shanghai Electronics Equipment Co., Ltd product)
7) blood gas analyzer (the portable blood gas analyzer of i-STAT U.S. Abbott Laboratories)
8) inverted phase contrast microscope (OLYMPUS IX7042)
9) supercentrifuge (U.S. Kendro Lab Prod GmbH)
10) automatic clinical chemistry analyzer (the sharp despot of Germany full automatic biochemical apparatus)
2 methods
2.1 experiment is prepared
All clinical medicine institute/West China hospital Technology Park anesthesia and critical first aid research department carry out all operations in the West China.
Drink is prohibited in the fasting evening before yesterday of laboratory animal art, morning, causes respiratory tract obst ruction in order to avoid cause after the anesthesia that gastric content backflows.Preoperative preserved skin, scope are that breastbone center and bilateral groin operative incision are the 10cm zone at center.Intramuscular injection half an hour atropine 0.02mg/kg before the art to reduce the tracheae endocrine, prevents airway obstruction, and fully exposes the tracheae opening when being convenient to intubate.
Earlier animal is fixed on the fixed mount before the anesthesia, puncture left upper extremity median basilic vein is inserted and fixing venous detaining needle the anesthesia of 3% yellow Jackets (25mg/kg) row vein, Benzylpenicillin sodium salt (2.5 ten thousand u/kg) intravenous injection prevention infection, and quiet equilibrium liquid.
Intravenous Anesthesia success back dog dorsal position, incidence is used the 7F silica gel trachea cannula of band air bag a little less than the health plane, and the artificial airway is set up in laryngoscope guiding direct-view oral trachea cannula down.Insertion depth is generally 22～26cm, coughs sound or when seeing that the trachea cannula inwall has fog to manifest with breathing, the success of expression intubate when hearing that dog has slightly to choke.Whether clear and symmetrical with the two pulmonary respiration sounds of auscultation with stethoscope, confirm the position of trachea cannula.Inject fixed air cannula behind the 5ml air in the intubate air bag, trachea cannula properly is fixed on the dog mouth with restraint strap.
Trachea cannula connects lung ventilator and carries out artificial Aided Machine ventilation, and ventilator parameter is set to: fraction of inspired oxygen 100%, respiratory rate 20 times/minute, tidal volume 15ml/kg.
Dog tongue card is put the oxygen saturation probe, and four limbs are kept somewhere the electrocardioelectrode sheet, connects life monitor.Row one side femoral artery puncture is put pipe, connects pressure transducer monitoring blood pressure.Each time point extraction arterial blood by research and design is carried out blood gas analysis.The capable central vein puncture and intubation of opposite side femoral vein is used for venous transfusion and gathers the venous blood sample.
2.2 experiment is divided into groups
This part experiment is divided into two groups: (the center open chest surgery is made the aorta ascendens interlayer controlled hypertension of pedestrian worker of going forward side by side to experimental group; 6); Control group (the chest controlled hypertension of pedestrian worker of going forward side by side is opened in the center, does not undergo surgery in the open chest surgery to make aorta ascendens interlayer, 6).
2.3 experimental group is set up the method for acute aorta clamp layer model
The routine disinfection drape, chest median incision is successively cut skin, subcutaneous, muscle layer, and scroll saw cuts breastbone, and the suspention pericardium exposes aorta ascendens.At the position of the about 2cm of aorta ascendens initial part far-end, sidewall pincers stringer clamp sustainer sidewall about 1/2 all footpaths, wide 1/2 of the aorta ascendens Zhou Jing that reaches of film in roundlet blade transection adventitia and the part.Find middle intermembrane space, unclamp the sidewall pincers, use intermembrane space in the Wen Shi tip clamp part edge, softly separate the about 1cm of lengthwise to the distal end passivity.Insert the Φ 2.5mm Micropump that connects syringe and prolong pipe, high pressure is injected physiological saline fast, utilizes the impact strength of physiological saline pressure to enlarge the interlayer scope, until the about 5cm of strip length.Inject elastin enzyme (200u adds 2ml physiological saline) in the false chamber, compressing sustainer otch makes it in false chamber, to keep somewhere about 5 minutes kinds.The clamp sidewall clamps once more; Cut the middle film and the inner membrance of internal layer, aorta lumen communicated with the external world, fan-shaped wipe out interlayer otch distal end partly in film and inner membrance; Film in 6-0prolene suturing with thread management otch proximal part aorta wall holostrome and distal end adventitia and the part makes blood can continue to get into false chamber.Unclamp the sidewall pincers, strengthen once more sewing up the incision, careful hemostasis.Interlayer completes, and successively closes chest, sews up the wall of the chest.Connect micro pump, vein pumps into adrenaline rising blood pressure.The adrenaline compound method is that body weight * 0.03mg of animal adds in the 50ml physiological saline, initially pumps into 2ml/h, according to the adrenergic amount of pumping into of systolic pressure adjustment, the laboratory animal systolic pressure is maintained between 250～260mmHg in the experimentation.
2.4 the method for building up of control group
Same experimental group is prepared in anesthesia and operation, and chest is opened in operation only row, the suspention pericardium, and clamp aorta ascendens wall and Artificial Control property hypertension are not carried out the operation of aorta ascendens interlayer and are made in the operation.Adrenaline is prepared and is pumped into method, the same experimental group of dosage adjustments, and the animal systolic pressure is maintained between 250～260mmHg.
2.5 the collection of blood preparation and detection
Gather: respectively at before the open chest surgery of anesthesia back (T1); When operation finishes (T2); Back 2 hours (T3) performs the operation; Perform the operation back 4 hours (T4), perform the operation back 6 hours (T5) totally 5 time points put from femoral artery puncture and gather ABS action arteries and veins blood gas analysis and the detection through the capable hepatic and renal function of central vein catheter venous blood samples sample the pipe.
Detect: arterial blood gas analysis: use disposable special-purpose arterial blood drawing pin, extract the 1ml arterial blood, in the portable blood gas analyzer of i-STAT U.S. Abbott Laboratories, detect and proofread and correct in 10 minutes according to body temperature.
Blood plasma: extracting vein blood 5ml inserts in the EDTA anticoagulant tube; Mixing; 3000 rev/mins of high speed centrifugations are 15 minutes then; Get supernatant liquid, 4 ℃ of refrigerator cold-storages are preserved, and in 1 week, send the detection of West China clinical medicine institute of Sichuan University/traditional Chinese medicine safety evaluatio center Biochemical Lab of West China hospital row hepatic and renal function.
2.6 the collection of Pathologic specimen and analysis
All laboratory animal all in operation back 6 hours (T5 time point) acute stages execution, are excised whole sustainers, dissect dissection of aorta statistics interlayer and tear length; Excision lung tissue (whole upper left lung), small intestine (arteria mesenterica anterior feed region), left half liver, the capable gross examination of skeletal muscle of left kidney, and keep fixing in dissection of aorta, lung, enteron aisle, liver and the kidney specimen formalin, preservation, the pathological section microscopically is observed.
3 statistical procedures
All measurement data data are all represented with mean ± standard deviation, use SPSS13.0 software and carry out statistical analysis, relatively adopt the t check of paired data between group, relatively adopt the q check of comparing in twos in the group.Inspection level is made as 0.05, and P＜0.05 is thought has significant difference.
Three results
1 General Result
18 of beagle dogs are used in this part experiment altogether, and wherein control group is 6; Remain 12 beagle dogs and make dissection of aorta.The early stage dissection of aorta of making of experiment is observed 6 of failures with experiment, and dog is dead 3 when wherein making dissection of aorta, and after dead dog was dissection of aorta and completes, the interlayer operative incision was sewed up anthemorrhagic difficulty, because of haemorrhagic shock dead; 3 of failures are observed in experiment, and it is bigger to be in the experimentation vital sign fluctuation, interrupts observing.Making the dissection of aorta success and accomplishing omnidistance 6 of the laboratory animal of observing is experimental group, and whole process is observed in control group operation and experiment does not all have death.
The body weight of each 6 dog of experimental group and control group, operating time, dissection of aorta Production Time, experiment overall process amount of infusion no difference of science of statistics (P＞0.05) are seen table 1.Wherein control group adopts and to open twice clamp sustainer behind the chest, and imitation interlayer manufacturing process also guarantees the uniformity of two groups of operating times.Interior each time point SAP of two treated animals experiment observation period is no difference of science of statistics (P＞0.05) also, sees table 2.
Table 1 experimental group and control group be
relatively
Table 2 experimental group and control group SAP (mmHg) be
relatively
2 laboratory animal pathology gross anatomies and microscopically are observed
2.1 the pathology gross anatomy of experimental group dissection of aorta and microscopically are observed
6 beagle dogs are successfully produced dissection of aorta and accomplish all experiment observations, see Fig. 1.The experimental group experiment finishes the back and dissects whole sustainers, and gross examination of skeletal muscle sees that it is 14.5～18.5cm that interlayer is torn length, average 17.67 ± 0.52cm; All dissection of aorta are torn all above diaphram, wherein 1 between diaphram and arteria mesenterica anterior, 3 between the arteria mesenterica anterior and the arteria renalis, 2 between the arteria renalis and common iliac artery.Microscopically is observed it is thus clear that dissection of aorta is torn and is arranged in the aorta wall lamellar spacing, and middle level elastorrhexis, and visible inflammatory cell infiltration are seen Fig. 2,3.
2.2 experimental group and the pathology gross anatomy of control group lung tissue and microscopically are observed
Gross examination of skeletal muscle: the experimental group left upper lobe of lung shows: stethemia, and oedema, color is gloomy, and volume increases, and whole water content increases, and has a large amount of edema with the lung involved to overflow when tangent plane is pushed, and sees Fig. 4.The control group left upper lobe of lung shows: lung is evenly rose pink, and coating is smooth, good springiness, and volume does not have increase, no water content increase, the tangent plane homogeneous is pushed the lung tangent plane and is not had edema with the lung involved and overflow, and sees Fig. 5.
Microscopic examination: the intra-alveolar edema of experimental group lung tissue, hemorrhage, alveolar septa broadening, a matter broadening and alveolar fracture, the surrounding tissue oedema is seen Fig. 6,8.The structural integrity of control group lung tissue, alveolar space is clear, and alveolar septum is complete, and no oedema is seen Fig. 7,9.
2.3 experimental group and the pathology gross anatomy of control group enteron aisle and microscopically are observed
Gross examination of skeletal muscle: the enteron aisle color of experimental group is gloomy, and wriggle weakness is seen Figure 10.The enteron aisle color of control group is scarlet, and wriggling is normal, sees Figure 11.
Microscopic examination: the enteron aisle fine hair of experimental group ruptures, comes off, and visible a little ulcer of enteron aisle inner wall surface is seen Figure 12,14.The enteron aisle inwall of control group does not see that ulcer forms, and fluff structures is complete, and marshalling is seen Figure 13,15.
2.4 experimental group and the gross anatomy of control group hepatic pathology and microscopically are observed
Experimental group and control group liver specimens gross examination of skeletal muscle see that all liver surface is smooth, and the experimental group liver is not seen obvious necrotic lesion, sees Figure 16,17.
Microscopic examination is compared with control group, and the experimental group liver cell does not see obvious destruction, and the lobuli hepatis structural integrity is seen Figure 18, and 19,20,21.
2.5 experimental group and the pathology gross anatomy of control group kidney and microscopically are observed
Gross examination of skeletal muscle sees that experimental group is compared with the control group Pathologic specimen not have obviously and changes that experimental group kidney coating is complete, and smooth surface is not seen obvious infarct focus, sees Figure 22,23.
Microscopic examination is compared with control group, and experimental group glomerulus structural integrity is not seen obvious pathological change, sees Figure 24, and 25,26,27.
3 laboratory observation indexs
3.1 experimental group and control group ABG are relatively
3.1.1 experimental group and control group PO
2(mmHg) relatively
Blood oxygen pressure (PO2), blood oxygen pressure are that expression is dissolved in the pressure that oxygen molecule produced in the blood.
Compare with control group, experimental group is (T1) before open chest surgery; The PO of (T2) when operation finishes
2(mmHg) compare not statistically significant (P＞0.05).And the PO of perform the operation back 2 hours (T3), perform the operation back 4 hours (T4), operation back 6 hours (T5)
2(mmHg) all reduce (P＜0.05), see table 3.
Compare experimental group PO in the group
2(mmHg) (T2) begins carrying out property decline, each time point PO afterwards when operation finishes
2(mmHg) all reduce (P＜0.05) than (T1) before the open chest surgery.
Compare PO in the control group group
2(mmHg) each time point does not have obvious change, sees table 3.
Table 3 experimental group and control group PO2 (mmHg) be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
3.1.2 experimental group and control group SO
2Blood oxygen saturation (%) relatively
Relatively reach between experimental group and control group group in the group and compare,, see table 4 in the equal no difference of science of statistics of each time point (P＞0.05).
Table 4 experimental group and control group SO2 (%) be
relatively
3.1.3 experimental group and control group PCO
2Partial pressure of carbon dioxide (mmHg) relatively
Compare the PCO of experimental group T1, T2, T3 time point with control group
2(mmHg) no difference of science of statistics (P＞0.05), and in T4, T5 time point PCO
2(mmHg) increase, compared significant difference (P＜0.05), seen table 5 for two groups.
Relatively more visible in the experimental group group at operation end back PCO
2(mmHg) begin the rising of carrying out property, though the T3 time point is compared no difference of science of statistics with the T1 time point, make progress in time, both compare and begin that promptly significant difference is arranged (P＜0.05) to the T4 time point, to T5 time point significant difference remarkable (P＜0.01).Relatively, operation finishes each time point PCO of back in the control group group
2(mmHg) though rising is also arranged, each time point is compared equal no difference of science of statistics (P＞0.05) with the T1 time point, see table 5.
Table 5 experimental group and control group PCO
2(mmHg) relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
3.1.4 experimental group and control group TCO2 arterial blood total carbon dioxide capacity (mmol/l) are relatively
Relatively reach between experimental group and control group group in the group and compare,, see table 6 at the equal no difference of science of statistics (P＞0.05) of each time point TCO2 (mmol/l).
Table 6 experimental group and control group TCO2 (mmol/l) be
relatively
3.1.5 experimental group and control group HCO
3 -Blood gas analysis blood plasma (mmol/l) relatively
Relatively reach between experimental group and control group group in the group and compare, at each time point HCO
3 -(mmol/l) equal no difference of science of statistics (P＞0.05) is seen table 7.
Table 7 experimental group and control group HCO
3 -(mmol/l) relatively
3.1.6 experimental group and control group PH are relatively
Compare with control group, the equal not statistically significant of PH difference (P＞0.05) of experimental group T1, T2, T3, T4 time point, but significant difference is arranged in two groups of comparison PH of T5 time point, experimental group PH sees table 8 than control group low (P＜0.05).
Relatively more visible in the experimental group group, after operation finished, PH began to descend, and began to have compared with the T1 time point significant difference (P＜0.05) in the T3 time point; Make progress in time, T4, T5 time point PH are all than T1 time point significant difference obvious (P＜0.01).Relatively more visible in the control group group, after operation finished, T3, T4, also carrying out property decline of T5 time point control group PH had significant difference (P＜0.05); But compare with experimental group, the PH downward trend of control group is slow slightly, and in the T5 time point recovery trend is arranged, and sees table 8.
Table 8 experimental group and control group PH be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
3.1.7 experimental group and control group BE (buffuer excess) are relatively
Relatively reach between experimental group and control group group in the group and compare,, see table 9 at the equal no difference of science of statistics of each time point BE (P＞0.05).
Table 9 experimental group and control group BE be
relatively
3.2 experimental group and control group liver function are relatively
3.2.1 experimental group and control group A LT (U/L) are relatively
With control group relatively, experimental group is at the ALT of T1, T2, T3 time point (U/L) difference not statistically significant, and obviously raises (P＜0.05) at the ALT of T4, T5 time point (U/L), sees table 10.
Relatively more visible in the group, the ALT (U/L) that finishes the back experimental group at operation begins to raise, and has compared significant difference (P＜0.05) with the T1 time point in the ALT of T4, T5 time point (U/L).Each time point of the ALT of control group (U/L) does not have obvious change, sees table 10.
Table 10 experimental group and control group A LT (U/L) be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
3.2.2 experimental group and control group A ST (U/L) are relatively
Compare with control group, experimental group is compared the difference not statistically significant at the AST of T1, T2 time point (U/L), and obviously raises (P＜0.05) at the AST of T3, T4, T5 time point (U/L), sees table 11.
Relatively more visible in the group, AST (U/L) beginning that finishes the back experimental group in operation sharply raises, though at T3 time point not statistically significant (P＞0.05) still, compared significant difference (P＜0.05) with T1 in the AST of T4, T5 time point (U/L).Each time point of the ALT of control group (U/L) does not have obvious change, sees table 11.
Table 11 experimental group and control group A ST (U/L) be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
3.3 experimental group and control group renal function are relatively
3.3.1 experimental group and control group CREA creatinine (umol/l) are relatively
Compare with control group, experimental group is compared the difference not statistically significant at the CREA of T1, T2 (umol/l), and all significantly raises (P＜0.05) at the CREA of T3, T4, T5 time point (umol/l), sees table 12.
Relatively more visible in the experimental group group, when operation finishes (T2), the CREA of dog (umol/l) begins to raise, and the CREA (umol/l) of T4, T5 time point relatively has significant difference (P＜0.05) with the T1 time point.Control group CREA (umol/l) does not have obviously change, and each time point does not have significant difference, sees table 12.
Table 12 experimental group and control group CREA (umol/l) be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
3.3.2 experimental group and control group BUN urea nitrogen (umol/l) are relatively
Compare with control group, experimental group is compared the difference not statistically significant at the BUN of T1, T2 time point (umol/l), and obviously increases (P＜0.05) at the BUN of T3, T4, T5 time point (umol/l), sees table 13.
Relatively more visible in the experimental group group, the T2 time point begins, and the BUN of dog (umol/l) obviously rises, and T3, T4, T5 time point significantly increase (P＜0.05) than the BUN (umol/l) of T1 time point.Control group BUN (umol/l) does not have obviously change, and each time point does not have significant difference, sees table 13.
Table 13 experimental group and control group BUN (umol/l) be
relatively
Annotate: relatively, compare with experimental group: * P＜0.05, * * P＜0.01 between group
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
Four discuss
1, originally zoologizes the evaluation of model
6 Beagle dogs of this group are successfully produced with the acute Stanford A type dissection of aorta of MODS and accomplish omnidistance experiment and observe.Pathology gross anatomy of laboratory animal sustainer and microscopically are observed and confirmed: the operation improvement method of this experiment innovation and Artificial Control property hypertension have reached the result of anticipation when making animal model, in 6 hours acute stage, have formed the interlayer and the false chamber of sufficient length and width.
About defining of animal model MODS, the foreign literature report is not seen concrete indication.The 304 Hu Sen of hospital of PLA etc. thinks, the standard that desirable MODS animal model that meets clinical practice should possess is: the 1. common inducement basically identical of Risk Factors and clinical MODS; 2. the performance of SIRS is arranged; The functional disorder that 3. 2 above organs or system are arranged; 4. enough M & Ms are arranged.Because lung's capillary network is abundant, is the organ of accepting systemic blood, so lungs tend to become the target organ that suffers inflammatory damage at first, also are that the Insufficient internal organs of organ take place the most easily.In this experiment, the lung tissue of experimental group dissects gross examination of skeletal muscle and sees that lung tissue is congested, oedema; Microscopically is observed and can be seen that also alveolar destroys a matter broadening.Blood gas analysis is found, experimental group PO
2After operation finishes, begin the decline of carrying out property, T3, T4, T5 time point all significantly reduce (P＜0.05) than control group; Simultaneously, experimental group PCO
2Finish the back at operation and rise, T4, T5 time point obviously increase (P＜0.05) than control group.Explain that back dog lung tissue takes place interlayer and PFT receives inflammatory damage.In the experimentation, along with course of disease time progress, the enteron aisle colour-darkening, wriggle weakness, postoperative enteron aisle dissec are found the intestinal villus fracture, are come off, and these prove that all enteron aisle has also received damage.Though the tissue specimen of liver kidney is observed the evidence of not finding strong internal organs anatomical lesion; But the mensuration through hepatic and renal function is found; The lab index of reflection hepatic and renal functions such as experimental group ALT, AST, CREA, BUN is carrying out property rising after operation finishes all, with control group comparing difference remarkable (P＜0.05).Explain that hepatic and renal function also suffers tangible infringement.This shows that the animal model of the acute Stanford A type dissection of aorta that this experiment is made is at short notice with tangible MODS.This animal model has the success rate of operation height, and making is easier to, and the multiple organ injury that occurs together is obvious, and timeliness is remarkable, observes advantages such as convenient.Can become the outstanding animal model of the acute AD cause of disease of future studies, pathogenesis and intervention scheme, and be used widely.
Embodiment 2 utilizes the classical medicine checking animal model of the present invention of the acute Stanford A type dissection of aorta companion of treatment MODS and tentatively sets up related drugs screening system
1., set up acute Stanford A type dissection of aorta companion MODS animal model by embodiment 1 described method;
2., will treat acute Stanford A type dissection of aorta accompanies classical medicine, the drug candidate of MODS to be applied to animal model respectively;
3., compare with the classical medicine of the acute Stanford A type dissection of aorta companion of treatment MODS; Observe the influence situation of drug candidate to acute Stanford A type dissection of aorta companion MODS; And symptom, index are improved situation; And mark, estimate the medicine of the acute Stanford A of potential treatment type dissection of aorta companion MODS, verified that also animal model of the present invention is used for the feasibility of drug screening.
Through the evaluation of step c, classical medicine can obviously improve the symptom of model monkeys, proves animal model modeling success of the present invention, has proved that also this drug screening system is effective simultaneously.
Through the evaluation of step c, if drug candidate has improvement to the sick symptom of above-mentioned model or index, and reach the evaluation criterion of similar classic treatment medicine, prove that promptly this drug candidate has the effect of the acute Stanford A type dissection of aorta companion of treatment MODS.
Experimental example 3 rheum officinales are to the protective effect of acute Stanford A type dissection of aorta companion MODS organ
1 material
1.1 laboratory animal
12 of healthy adult Beagle dogs, male and female are regardless of, body weight 8～12kg, average 8.88 ± 0.80kg.Every animal divides cage solely to support before the art, and 23～25 ℃ of room temperatures are freely ingested, intake, 12 hours illumination/dark.Dog is provided by West China clinical medicine institute of Sichuan University/West China hospital traditional Chinese medicine safety evaluatio center, and is raised by laboratory animal requirement special messenger by West China clinical medicine institute of Sichuan University/West China hospital Experimental Animal Center Animal House.
1.2 main experiment reagent and medicine
1) liquaemin (biochemical-pharmaceutical factory, Shanghai)
2) Benzylpenicillin sodium salt (North China pharmacy)
3) adrenaline (Shanghai Hefeng Pharmaceutical Co., Ltd.)
4) yellow Jackets (Shanghai chemical reagents corporation)
5) atropine (Haiyang, Hangzhou medication chemistry Co., Ltd)
6) IL-6 kit (U.S. R&D company)
7) IL-10 kit (U.S. R&D company)
8) TNF-α kit (U.S. R&D company)
9) endotoxin tachypleus amebocyte lysate box (Kingsoft, Beijing river company)
10) archen (Jiangsu is risen imperial bio tech ltd and provided)
1.3 main experimental instrument and equipment
1) operating theater instruments (Shanghai gold clock medical apparatus corporation, Ltd)
2) electric knife (U.S.'s Willie electric knife)
3) electric suction apparatus (Shanghai medicine equipment industry company)
4) Anesthesia machine (Excel 210 SE Datex-Ohmeda)
5) micro-injection pump (Anji, Shanghai Electronics Equipment Co., Ltd product)
6) blood gas analyzer (i-STAT U.S. Abbott Laboratories palm blood gas analyzer)
7) inverted phase contrast microscope (OLYMPUS IX7042)
8) supercentrifuge (U.S. Kendro Lab Prod GmbH)
9) 721 spectrophotometric colour comparatours (German Luo Weibang company)
10) automatic clinical chemistry analyzer (the sharp despot of Germany full automatic biochemical apparatus)
2 methods
2.1 experiment is prepared
See experimental example 1.
2.2 experiment is divided into groups
This part experiment is divided into two groups: (the center open chest surgery is made the aorta ascendens interlayer controlled hypertension of pedestrian worker of going forward side by side to experimental group; 6) and organ protection agent group (the center open chest surgery is made the aorta ascendens interlayer controlled hypertension of pedestrian worker of going forward side by side; Finish back rising blood pressure simultaneously in operation; Archen 200mg/kg adds retention enema in the 20ml physiological saline, 6).
2.3 method for establishing model
See first.
2.4 the collection of blood preparation and detection
Gather: respectively at (T1) before the open chest surgery; When operation finishes (T2); Perform the operation back 2 hours (T3) perform the operation back 4 hours (T4), the detection of perform the operation back 6 hours (T5) 5 time points collections ABS action arteries and veins blood gas analysis and the capable hepatic and renal function of venous blood sample, endotoxin, cell factor.
Detection method is seen first and second part.
2.5 the collection of Pathologic specimen and analysis
All laboratory animal are all finished the execution of back 6 hours (T5 time point) acute stages in operation, excise whole sustainers, dissect dissection of aorta statistics interlayer and tear length; Excision lung tissue (upper left lung), small intestine (arteria mesenterica anterior feed region) carry out gross examination of skeletal muscle and make the slice row microscopically and observe.
3 statistical procedures
All measurement data data are all represented with mean scholar standard deviation, use SPSS13.0 software and carry out statistical analysis, relatively adopt the t check of paired data between group, relatively adopt the q check of comparing in twos in the group.Inspection level is made as 0.05, and P＜0.05 is thought has significant difference.
Three results
1 experimental group and organ protection agent group are relatively
The body weight of each 6 dog of experimental group and organ protection agent group dog, operating time, dissection of aorta Production Time, experiment overall process amount of infusion no difference of science of statistics, interlayer are torn more also no difference of science of statistics of two groups of length, see table 14.Two treated animals SAP no difference of science of statistics in the experiment observation period is seen table 15.
Table 14 experimental group and organ protection agent group be
relatively
Table 15 experimental group and organ protection agent group systolic pressure (mmHg) be
relatively
2 laboratory animal pathology gross anatomies and microscopically are observed
2.1 experimental group and the enteron aisle pathology gross anatomy of organ protection agent group and microscopically are observed
Gross anatomy is observed: experimental group: color is gloomy, and wriggling obviously weakens, and sees Figure 28.Organ protection agent group: smooth surface, color is scarlet than experimental group, and wriggling weakens slightly, sees Figure 29.
Microscopic examination: experimental group: the intestinal villi mucous membrane obviously ruptures, and the visible basilar memebrane that comes off is seen Figure 30,32.Organ protection agent group: only limit to the fracture of minority intestinal villi mucous membrane, quantity obviously reduces than experimental group, sees Figure 31, and 33.
2.2 experimental group and the lung tissue pathology gross anatomy of organ protection agent group and microscopically are observed
Gross anatomy is observed: the lung of experimental group is congested, oedema, and volume increases, and whole water content increases, and has a large amount of edema with the lung involved to overflow when tangent plane is pushed, and sees Figure 34.The lung color of organ protection agent group is scarlet than experimental group, and coating is more smooth, and visible a little the sick kitchen range that decreases in surface is pushed a little edema with the lung involved of lung tangent plane and overflowed, and sees Figure 35.Microscopic examination: the intra-alveolar edema of experimental group, hemorrhage, alveolar septa broadening, visible oozing out, a matter broadening and alveolar fracture, the surrounding tissue oedema is seen Figure 36,38.The alveolar septum broadening of organ protection agent group is few than experimental group, and alveolar septum is comparatively complete, and cellular infiltration is few than experimental group, sees Figure 37, and 39.
3 laboratory observation indexs
3.1 experimental group and organ protection agent group ABG are relatively
3.1.1 experimental group and organ protection agent group PO
2(mmHg) relatively
Compare organ protection agent group PO with experimental group
2(mmHg) in T1, T2, T3 time point indifference, but T4, T5 time point PO
2(mmHg) take a turn for the better (P＜0.05) than experimental group, see table 16.
Relatively more visible in the group, experimental group PO
2(mmHg) finish the back continuation at operation and descend, trend is obvious, and T3, T4, T5 time point all have significant difference (P＜0.05).Organ protection agent group PO
2(mmHg) downward trend is also arranged, the T4 time point has statistical significance (P＜0.05), but owing to there is the protective effect of archen, downward trend is slow than experimental group, and in T5 time point PO
2(mmHg) recover normal again, see table 16.
Table 16 experimental group and organ protection agent group PO
2(mmHg) relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
3.1.2 experimental group and organ protection agent group PCO
2(mmHg) relatively
Compare organ protection agent group PCO with experimental group
2(mmHg) in T1, T2, T3 time point indifference, but T4, T5 time point PCO
2(mmHg) take a turn for the better (P＜0.05) than experimental group, see table 17.
Relatively more visible in the group, experimental group PCO
2(mmHg) produce the back continuation at interlayer and rise, trend is obvious, in T4, T5 time point statistical significance (P＜0.05) is arranged all.Organ protection agent group PCO
2(mmHg) though also on the rise, owing to there is the protective effect of archen, operation finishes back each time point PCO
2(mmHg) with the relatively more equal no difference of science of statistics (P＞0.05) of T1 time point, see table 17.
Table 17 experimental group and organ protection agent group PCO
2(mmHg) relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
3.2 experimental group and organ protection agent group liver function are relatively
3.2.1 experimental group and organ protection agent group ALT (U/L) are relatively
Compare with experimental group; Organ protection agent group ALT (U/L) is in T1, T2 time point indifference; And compare still no difference of science of statistics (P＞0.05) for two groups in T3, T4 time point; But back 6 hours (T5) two groups have compared significant difference in operation, and organ protection agent group is seen table 18 than experimental group ALT (U/L) concentration low (P＜0.05).
Relatively more visible in the group, experimental group ALT (U/L) begins to raise after interlayer completes, and trend is obvious, and has compared significant difference (P＜0.05) with the T1 time point in T4, T5 time point.Organ protection agent group ALT (U/L) though rising is also arranged after interlayer completes, but trend is faint, and does not have significant difference all the time, sees table 18.
Table 18 experimental group and organ protection agent group ALT (U/L) be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
3.2.2 experimental group and organ protection agent group AST (U/L) are relatively
Compare with experimental group; Organ protection agent group AST (U/L) is in T1, T2 time point indifference; And compare still no difference of science of statistics (P＞0.05) for two groups in T3, T4 time point; But back 6 hours (T5) two groups have compared significant difference in operation, and organ protection agent group is seen table 19 than experimental group AST (U/L) concentration low (P＜0.05).
Relatively more visible in the group, experimental group AST (U/L) begins to rise after interlayer completes, and trend is obvious, and has all compared significant difference (P＜0.05) with the T1 time point in T3, T4, T5 time point.Organ protection agent group AST (U/L) also has rising after interlayer completes, but trend is milder, and the rising peak postpones, and only in T4, T5 time point significant difference (P＜0.05) is arranged, and sees table 19.
Table 19 experimental group and organ protection agent group AST (U/L) be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
3.3 experimental group and organ protection agent group renal function are relatively
3.3.1 experimental group and organ protection agent group CREA (umol/l) are relatively
Compare with experimental group, organ protection agent group CREA (umol/l) is in T1, T2 time point indifference, but T3, T4, T5 time point have been compared significant difference for two groups after operation finishes, and organ protection agent group is seen table 20 than experimental group low (P＜0.05).
Relatively more visible in the group, experimental group CREA (umol/l) begins to rise after interlayer completes, and trend is obvious, and has compared significant difference (P＜0.05) with the T1 time point in T4, T5 time point.Organ protection agent group CREA (umol/l) does not have significant change in the interlayer back concentration that completes, and each time point equal no difference of science of statistics of comparing with the T1 time point is seen table 20.
Table 20 experimental group and organ protection agent group CREA (umol/l) be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
3.3.2 experimental group and organ protection agent group BUN (umol/l) are relatively
BUN (umol/l) compares T1, T2 time point indifference for two groups; And compare still no difference of science of statistics for two groups in T3, T4 time point; Compared significant difference for two groups but finish back 6 hours (T5) in operation, organ protection agent group is seen table 21 than experimental group low (P＜0.05).
Relatively more visible in the group, experimental group BUN (umol/l) begins to raise after interlayer completes, and trend is obvious, and the T3 after interlayer completes, T4, T5 time point are compared with the T1 time point all has significant difference (P＜0.05).Organ protection agent group BUN (umol/l) also has rising trend after interlayer completes, the equal no difference of science of statistics (P＞0.05) but each time point is compared with the T1 time point is seen table 21.
Table 21 experimental group and organ protection agent group BUN (umol/l) be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
4 experimental group and organ protection agent group endotoxin and cell factor are relatively
4.1 experimental group and organ protection agent group endotoxin (pg/ml) are relatively
Experimental group is compared no difference of science of statistics with organ protection agent group endotoxin (pg/ml) in T1, T2 time point; But organ protection agent group endotoxin (pg/ml) three time points of T3, T4, T5 after the rheum officinale protectant begins are seen table 22 all than experimental group low (P＜0.05).
Relatively more visible in the group, experimental group endotoxin (pg/ml) sharply rises after interlayer completes, and trend is obvious, and the T3 after interlayer completes, T4, T5 time point are compared significant difference obviously (P＜0.01) with the T1 time point.Organ protection agent group endotoxin (pg/ml) is accomplished back rising trend also clearly in operation, but with experimental group relatively it is thus clear that its rising speed is slow slightly, see table 22.
Table 22 experimental group and organ protection agent group endotoxin (pg/ml) be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
4.2 experimental group and organ protection agent group cell factor are relatively
4.2.1 experimental group and organ protection agent group TNF-α (ug/ml) are relatively
Two groups of TNF-α (ug/ml) compare, and in T1, T2 time point indifference, but T3, T4, T5 time point are compared for two groups after the archen protectant, and organ protection agent group TNF-α (ug/ml) is low than experimental group, and significant difference is (P＜0.01) significantly, sees table 23.
Relatively more visible in the group, experimental group TNF-α (ug/ml) sharply raises after operation is accomplished, and trend is obvious, and T3, T4, T5 time point are compared significant difference significantly (P＜0.01) with the T1 time point.Although organ protection agent group TNF-α (ug/ml) completes back rising trend also clearly in interlayer, slow slightly with relatively more visible its rising speed of experimental group, see table 23.
Table 23 experimental group and organ protection agent group TNF-α (ug/ml) be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
4.2.2 experimental group and organ protection agent group IL-6 (ug/ml) are relatively
Two groups of IL-6 (ug/ml) compare, and in T1, T2 time point indifference, but T3, T4, T5 time point are compared for two groups after the archen protectant, and organ protection agent group IL-6 (ug/ml) is low than experimental group, and significant difference is (P＜0.01) significantly, sees table 24.
Relatively more visible in the group, experimental group IL-6 (ug/ml) sharply rises after operation is accomplished, and trend is obvious, and T3, T4, T5 time point are compared significant difference significantly (P＜0.01) with the T1 time point.Organ protection agent group IL-6 (ug/ml) is also on the rise after operation is accomplished, but slow slightly with relatively more visible its rate of climb of experimental group, and only in T5 time point and T1 time point significant difference (P＜0.05) is arranged, and sees table 24.
Table 24 experimental group and organ protection agent group IL-6 (ug/ml) be
relatively
Annotate: relatively, compare between group with experimental group:
*P＜0.05,
*P＜0.01
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
4.2.3 experimental group and organ protection agent group IL-10 (ug/ml) are relatively
Two groups of IL-10 (ug/ml) relatively; In T1, T2 time point indifference; And in testing still no difference of science of statistics (P＞0.05) of end back T3, T4 time point; Only compared significant difference (P＜0.05) in two groups of T5 time points, organ protection agent group reduces than experimental group IL-10 (ug/ml) content, sees table 25.
Relatively more visible in the group, experimental group IL-10 (ug/ml) sharply rises after operation is accomplished, and trend is obvious, and T3, T4, T5 time point are compared significant difference significantly (P＜0.01) with the T1 time point.Organ protection agent group IL-10 (ug/ml) is also on the rise after interlayer completes, but slow slightly with relatively more visible its rising speed of experimental group, sees table 25.
Table 25 experimental group and organ protection agent group IL-10 (ug/ml) be
relatively
Annotate: relatively, compare with experimental group: * P＜0.05, * * P＜0.01 between group
Relatively, compare in the group with the T1 time point:
△P＜0.05,
△ △P＜0.01
Four discuss
The effect of 1 rheum officinale in SIRS and MODS
The organ protection agent that this experiment adopts the active ingredient emodin in the Chinese herb rhubarb to accompany MODS as acute Stanford A type dissection of aorta.
The observed result of 2 researchs
2.1 archen is to the protective effect of enteron aisle
After using the archen bowel lavage, the blood of organ protection agent group dog enteron aisle supplies to increase, and wriggling strengthens, and the enteron aisle surface is smooth than experimental group, and color is scarlet; Experiment finishes back sample microscopically to be observed and can see, intestinal mucosa is preserved comparatively complete, and the fine hair fracture reduces.Explain that archen has good protective action to enteron aisle.
2.2 archen is to the protective effect of lung
After using the archen bowel lavage, organ protection agent group pulmonary edema alleviates; Microscopically is observed and can be seen, alveolar septum is preserved comparatively complete, destroys and reduces, and cellular infiltration is few.Blood gas analysis simultaneously also can see, after the archen bowel lavage, and the PO of organ protection agent group
2Downward trend weakens, and on the rise at the T5 time point, reaches 385.33 ± 57.18mmHg, obviously increases (P＜0.01) than experimental group; Organ protection agent group PCO
2Rising trend weakens, with the T1 time point relatively, other times point is no difference of science of statistics (P＞0.05) all the time all.Explain that archen has produced good protective action to lung.
2.3 archen is to the protective effect of hepatic and renal function
After using the archen bowel lavage, organ protection agent group ALT rising trend weakens, and compares with the T1 time point, puts equal no difference of science of statistics (P＞0.05) At All Other Times; Organ protection agent group AST rising trend weakens, and only in T4, T5 time point and T1 time point significant difference (P＜0.05) is arranged relatively.Organ protection agent group CREA does not have significant change, each time point equal no difference of science of statistics (P＞0.05) of comparing with the T1 time point in the interlayer back concentration that completes; BUN also has rising after interlayer completes, but compares with experimental group, and each time point rises and all weakens, and interior relatively each time point of group and the relatively more equal no difference of science of statistics (P＞0.05) of T1 time point.Explain that archen has also produced good protective action to hepatic and renal function, reduced ALT, AST, CREA and the BUN concentration in blood.
2.4 archen is to endotoxic protective effect
Though organ protection agent group endotoxin also sharply increases after interlayer completes; T3, T4, T5 time point are respectively 53.73 ± 16.26pg/ml, 58.72 ± 5.69pg/ml, 73.12 ± 15.17pg/ml; But the amplitude that increases weakens than experimental group, and endotoxin content all reduces (P＜0.05) than experimental group.Explain that archen can effectively reduce endotoxin and go into blood.
2.5 the protective effect of the archen pair cell factor
Organ protection agent group TNF-α, IL-6 ascendant trend after the archen bowel lavage weaken, and T3, T4, T5 time point and experimental group comparison content obviously reduce (P＜0.01).Though the IL-10 of organ protection agent group still sharply increases after operation finishes, weaken with relatively increase trend of experimental group, the T5 time point reduces (P＜0.05) than experimental group content.Explain that archen can reduce the release of cell factor in blood.
3 rheum officinales are to the mechanism of each organ protection
Research shows that enteron aisle is not only the target organ of MODS; One of startup organ of MODS especially; And lung is the main release organ and the target organ of cell factor, and these two important organs are interrelated, common formation " intestines-lung reaction axle "; Inflammatory reaction is amplified, thereby each internal organs of whole body are caused damage.Our tentative confirmation in first experiment, behind acute dissection of aorta, since the enteron aisle ischemic, the intestinal mucosal barrier damage; Simultaneously PFT also suffers damage, and then hepatic and renal function suffers destruction in various degree, and MODS has taken place.Therefore, " intestines-lung reaction axle " play an important role in MODS generation and evolution.To effectively protect the whole body function, at first will effectively protect, and then interrupt " intestines-lung reaction axle " promotion MODS to the intestines barrier.
Archen can effectively be protected intestinal mucosal barrier, increases enteron aisle blood and supplies, and promotes intestines peristalsis, thereby intestinal endotoxin is excreted.And archen can significantly suppress mononuclear macrophage TNF secretion-α, the IL that endotoxin is induced, and has damage of the cell factor of inhibition and inflammatory mediator and enhancing body immunity function, thereby stops the generation of MODS.In this research, finish the back at operation and use the archen bowel lavage, supply because archen can significantly increase the blood of enteron aisle; Promote the wriggling of enteron aisle; Protected intestinal mucosal barrier, the inflammatory cell that gets into lung tissue reduces, and has interrupted " intestines-lung reaction axle " cascade amplification to systemic inflammatory response; The damage of whole body organ weakens, and organ function has obtained excellent protection.Simultaneously, after the archen bowel lavage, owing to effectively protected intestinal mucosal barrier; Bacterium and endotoxic displacement have been reduced; Endotoxin reduces in the organ protection agent group blood, thereby has reduced the outburst that causes cell factor owing to endotoxic a large amount of releases, and we observe; TNF-α, IL-6, IL-10 ascensional range all weaken, and content reduces.Therefore, archen has effectively suppressed inflammatory reaction, has alleviated SIRS.
In a word; Archen can promote the wriggling of enteron aisle, the protection gastrointestinal barrier, thus function of intestinal canal is played a protective role; Reduce intestines source property toxin and get into blood or lymph liquid; Reduce the activation of cell factor, blocking-up endotoxin and cell factor are through portal vein or directly flow into pulmonary circulation and body circulation by intestines lymph approach, alleviate SIRS.Archen still can directly reduce the expression of TNF-α, IL, thereby reduces the damage of inflammatory reaction to lungs, alleviates " intestines-lung axle " to the cascade amplification of inflammatory reaction, interrupts inflammatory pathology association between internal organs, in case be far apart the organ dysfunction damage.This shows that archen can be protected the function of important organ under the pathologic condition, assist to safeguard balance, coordination and restricting relation between each internal organs.
Claims (8)
1. the method for building up of an acute Stanford A type dissection of aorta companion MODS animal model, it comprises the steps:
A, get experimental dog, expose aorta ascendens;
B, at the position of aorta ascendens initial part far-end 2cm, sidewall pincers stringer clamp sustainer 1/2 week of sidewall the footpath, wide 1/2 of the aorta ascendens Zhou Jing that reaches of film in roundlet blade transection adventitia and the part; Find middle intermembrane space, unclamp the sidewall pincers, use intermembrane space in the Wen Shi tip clamp part edge, softly separate lengthwise 1cm to the distal end passivity;
The Φ 2.5mm Micropump that c, insertion connect syringe prolongs pipe, and high pressure is injected physiological saline fast, utilizes the impact strength of physiological saline pressure to enlarge the interlayer scope, until strip length 5cm; Inject elastin enzyme (200u adds 2ml physiological saline) in the false chamber, compressing sustainer otch makes it in false chamber, to keep somewhere 5 fens kinds;
D, clamp sidewall pincers once more; Cut the middle film and the inner membrance of internal layer; Aorta lumen is communicated with the external world; Fan-shapedly wipe out film and inner membrance in the interlayer otch distal end part, film in 6-0prolene suturing with thread management otch proximal part aorta wall holostrome and distal end adventitia and the part makes blood can continue to get into false chamber;
E, unclamp sidewall pincers, strengthen sewing up the incision hemostasis once more; Interlayer completes, and successively closes chest, sews up the wall of the chest;
F, connection micro pump, vein pumps into adrenaline rising blood pressure, and the laboratory animal systolic pressure is maintained between 250～260mmHg.
2. the animal model of the described method preparation of claim 1 is treated acute Stanford A type dissection of aorta in screening and is accompanied the purposes in the medicine of MODS.
3. a method of screening the acute Stanford A type dissection of aorta companion of treatment MODS medicine comprises the steps:
1., set up acute Stanford A type dissection of aorta companion MODS animal model;
2., will treat acute Stanford A type dissection of aorta accompanies medicine, the drug candidate of MODS to be applied to animal model respectively;
3., observe the influence situation of drug candidate to acute Stanford A type dissection of aorta companion MODS, and mark, estimate the medicine of the acute Stanford A of potential treatment type dissection of aorta companion MODS.
4. screening technique according to claim 3 is characterized in that: 1. the method for building up of the described acute Stanford A type dissection of aorta companion MODS animal model of step is:
A, get experimental dog, expose aorta ascendens;
B, at the position of aorta ascendens initial part far-end 2cm, sidewall pincers stringer clamp sustainer 1/2 week of sidewall the footpath, wide 1/2 of the aorta ascendens Zhou Jing that reaches of film in roundlet blade transection adventitia and the part; Find middle intermembrane space, unclamp the sidewall pincers, use intermembrane space in the Wen Shi tip clamp part edge, softly separate lengthwise 1cm to the distal end passivity;
The Φ 2.5mm Micropump that c, insertion connect syringe prolongs pipe, and high pressure is injected physiological saline fast, utilizes the impact strength of physiological saline pressure to enlarge the interlayer scope, until strip length 5cm; Inject elastin enzyme (200u adds 2ml physiological saline) in the false chamber, compressing sustainer otch makes it in false chamber, to keep somewhere 5 fens kinds;
D, clamp sidewall pincers once more; Cut the middle film and the inner membrance of internal layer; Aorta lumen is communicated with the external world; Fan-shapedly wipe out film and inner membrance in the interlayer otch distal end part, film in 6-0prolene suturing with thread management otch proximal part aorta wall holostrome and distal end adventitia and the part makes blood can continue to get into false chamber;
E, unclamp sidewall pincers, strengthen sewing up the incision hemostasis once more; Interlayer completes, and successively closes chest, sews up the wall of the chest;
F, connection micro pump, vein pumps into adrenaline rising blood pressure, and the laboratory animal systolic pressure is maintained between 250～260mmHg.
Archen in preparation as the purposes in the medicine of the organ protection agent of acute Stanford A type dissection of aorta companion MODS.
6. purposes according to claim 5 is characterized in that: the using dosage of archen is 200mg/kg in the described medicine.
7. the organ protection agent of an acute Stanford A type dissection of aorta companion MODS, it is that archen by effective dose is an active component, adds the preparation that acceptable accessories or complementary composition are prepared from.
8. organ protection agent according to claim 7 is characterized in that: described preparation is an oral formulations.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010608819 CN102334465B (en) | 2010-12-28 | 2010-12-28 | Application of emodin in preparing medicine for acute Stanford A-type aortic dissection (AD) prevention or organ protector accompanied with MODS (multiple organ dysfunction syndrome) |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010608819 CN102334465B (en) | 2010-12-28 | 2010-12-28 | Application of emodin in preparing medicine for acute Stanford A-type aortic dissection (AD) prevention or organ protector accompanied with MODS (multiple organ dysfunction syndrome) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102334465A true CN102334465A (en) | 2012-02-01 |
| CN102334465B CN102334465B (en) | 2013-06-05 |
Family
ID=45510607
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010608819 Expired - Fee Related CN102334465B (en) | 2010-12-28 | 2010-12-28 | Application of emodin in preparing medicine for acute Stanford A-type aortic dissection (AD) prevention or organ protector accompanied with MODS (multiple organ dysfunction syndrome) |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102334465B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103416352A (en) * | 2012-05-22 | 2013-12-04 | 浙江中医药大学 | Animal model of hypertension comprehensively caused by high-salt, high-sugar and high-fat diet |
| CN103416347A (en) * | 2012-05-22 | 2013-12-04 | 浙江中医药大学 | Lifestyle hypertension animal model caused by drinking and high-sugar high-fat diet |
| CN105232172A (en) * | 2015-10-30 | 2016-01-13 | 新疆医科大学第一附属医院 | A Stanford A type aortic dissection animal model and a method for manufacturing the same |
| CN112005950A (en) * | 2020-07-23 | 2020-12-01 | 湖南盛义建设有限公司 | Ecological farmland system and construction method thereof |
| CN112669687A (en) * | 2020-12-01 | 2021-04-16 | 大连理工大学 | Method for manufacturing personalized in-vitro interlayer physical model |
| CN113611201A (en) * | 2021-08-13 | 2021-11-05 | 贾贺月 | Method for constructing aortic dissection model by adopting biological material |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2626567C1 (en) * | 2016-10-11 | 2017-07-28 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Сибирский государственный медицинский университет" Министерства здравоохранения Российской Федерации (ФГБОУ ВО СибГМУ Минздрава России) | Method for legg-calve-perthes disease simulation |
-
2010
- 2010-12-28 CN CN 201010608819 patent/CN102334465B/en not_active Expired - Fee Related
Non-Patent Citations (5)
| Title |
|---|
| 林胜璋等: "大黄素对大鼠肝脏缺血再灌注损伤的预防作用", 《中国中西医结合外科杂志》 * |
| 王春伟等: "大黄素对大鼠重症急性胰腺炎肠黏膜的保护作用", 《浙江医学》 * |
| 胡学文等: "大黄素、川芎嗪对家兔低血容量性休克再灌注多脏器功能损害的影响", 《咸宁学院学报（医学版）》 * |
| 苏月南等: "全身炎症反应综合征的靶器官保护", 《中华急诊医学杂志》 * |
| 郑雨等: "大黄及大黄素干预全身性炎症反应作用的研究进展", 《中药材》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103416352A (en) * | 2012-05-22 | 2013-12-04 | 浙江中医药大学 | Animal model of hypertension comprehensively caused by high-salt, high-sugar and high-fat diet |
| CN103416347A (en) * | 2012-05-22 | 2013-12-04 | 浙江中医药大学 | Lifestyle hypertension animal model caused by drinking and high-sugar high-fat diet |
| CN105232172A (en) * | 2015-10-30 | 2016-01-13 | 新疆医科大学第一附属医院 | A Stanford A type aortic dissection animal model and a method for manufacturing the same |
| CN112005950A (en) * | 2020-07-23 | 2020-12-01 | 湖南盛义建设有限公司 | Ecological farmland system and construction method thereof |
| CN112005950B (en) * | 2020-07-23 | 2023-02-03 | 湖南盛义建设有限公司 | Ecological farmland system and construction method thereof |
| CN112669687A (en) * | 2020-12-01 | 2021-04-16 | 大连理工大学 | Method for manufacturing personalized in-vitro interlayer physical model |
| CN112669687B (en) * | 2020-12-01 | 2022-06-21 | 大连理工大学 | Method for manufacturing personalized in-vitro interlayer physical model |
| CN113611201A (en) * | 2021-08-13 | 2021-11-05 | 贾贺月 | Method for constructing aortic dissection model by adopting biological material |
| CN113611201B (en) * | 2021-08-13 | 2023-12-22 | 贾贺月 | Method for constructing aortic dissection model by adopting biological material |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102334465B (en) | 2013-06-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102334465B (en) | Application of emodin in preparing medicine for acute Stanford A-type aortic dissection (AD) prevention or organ protector accompanied with MODS (multiple organ dysfunction syndrome) | |
| CN105535001B (en) | Application of the rhodioside in the medicine for preparing treatment diabetes | |
| CN111920541A (en) | Method for constructing sepsis compound animal model | |
| Tong et al. | Respiratory Emergencies | |
| CN105943188A (en) | Method for establishing pig thoracic aorta dissection model | |
| Moon | The shock syndrome in medicine and surgery | |
| CN109620457A (en) | A kind of animal disease model of pinpoint chest, abdominal aneurvsm | |
| CN105287370B (en) | A kind of preparation method of inosine and combinations thereof composition injection | |
| CN113577102A (en) | Application of iron nanocluster in preparation of anti-septicemia and myocardial damage drug induced by same | |
| CN209075643U (en) | Special pipeline pre-filling circulating device for ECMO | |
| CN201524083U (en) | Disposable flexibly connected anticoagulant blood taking needle | |
| Zhao et al. | Risk factors and management of catheter malfunction during urgent-start peritoneal dialysis | |
| CN102077807A (en) | Preparation method of myocardial ischemia/reperfusion model in rats | |
| CN103340663A (en) | Capsule type coronary oppressing device and method for manufacturing chronic myocardial ischemia animal model | |
| Kong et al. | Safety of one 8.5-Fr pigtail catheter for postoperative continuous open gravity drainage after uniportal video-assisted thoracoscopic surgery pneumonectomy | |
| Wang et al. | Laparoscopic right hemicolectomy with transvaginal specimen extraction | |
| Dutra et al. | Intravascular access in Chelonia mydas and Dermochelys coriacea using the Seldinger technique ultrasound-guided | |
| Zhang et al. | Laparoscopic right hepatectomy via anterior approach: The experience at a single center | |
| MONOD et al. | Resection of an aneurysm of the arch of the aorta with preservation of the lumen of the vessel | |
| CN114796265A (en) | Application of S-nanoFe in preparation of anti-septicemia and myocardial damage drug induced by same | |
| CN107474030B (en) | Warfarin-aspirin conjugates, their synthesis, antithrombotic activity and uses | |
| RU2636177C1 (en) | Method for limited chronic pleural empyema simulation | |
| CN116918760A (en) | Construction method and application of severe wound/systemic inflammatory response model of mice | |
| Caponas et al. | Difficulty in use and device failure with the intubating laryngeal mask airway® | |
| Schwartzman et al. | Perioperative Evaluation of Arterial and Venous Whole Blood in the Lamb (Ovis aries) Fontan Model |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130605 Termination date: 20191228 |